The proposed research program will study the adverse effects of alcohol on cellular proliferation, maturation, protein synthesis and cell survival, especially as regards the effect of alcohol on pyridoxine and folate metabolism. Using both animal model and human protocol studies, specific mechanisms of alcohol toxicity on the availability, gut uptake, tissue uptake and storage, delivery and intracellular metabolism of folate and pyridoxine metabolites will be defined and characterized. The effect of alcohol on erythrocyte pyridoxine kinase activity, transaminase levels and intracellular availability of pyridoxal 5-phosphate will be studied in detail to improve understanding as to a potential alcohol effect of porphyrin metabolism. In the area of disturbed folic acid metabolism, investigations will be directed at a number of the steps of the enterohepatic folate cycle and the reduction, methylation and polyglutamate formation steps of folate storage in the liver. This work is aimed at a better understanding of the observed effect of alcohol on serum folate levels and the development of maturation defects in hematopoietic tissue. BIBLIOGRAPHIC REFERENCES: Hillman, R.S.: Alcohol and Hematopoiesis, NY Acad Sciences, 252:297, 1975. Piece, H.I., McGuffin, R. and Hillman, R.S.: Clinical Studies in Alcoholic Sideroblastosis. Arch. of Int. Med., 136:283, 1976.